Time-related changes in full-length hepatitis C virus sequences and hepatitis activity.
(57/3443)
The activity of hepatitis varies in chronic hepatitis C virus (HCV) infection. Some patients show persistently normal serum alanine aminotransferase (ALT) values, whereas the others show high-ALT values and progress to liver cirrhosis or hepatocellular carcinoma. However, virological mechanisms causing hepatitis have not fully been elucidated. We analyzed serial changes in full-length HCV sequences in 10 patients with various profiles of hepatitis activity. In the nonstructural 5A (NS5A) and NS5B, the rate of amino acid changes, as well as the proportion of nonsilent ones, was low in patients with normal ALT values compared with those with abnormal ALT (for the rate of amino acid changes, 0 x 10(-3) vs 3.19 x 10(-3) changes/site/year (P = 0.037) in NS5A and 0 x 10(-3) vs 1.22 x 10(-3) changes/site/year (P = 0.023) for NS5B, for the proportion of nonsilent changes, 4 vs 22% (P = 0.017) in NS5A and 0 vs 16% (P = 0. 039) in NS5B). Also, the flare-up of hepatitis coincided with higher nucleotide/amino acid substitution rates in NS5B. In conclusion, the genomic structures of the NS5A and NS5B regions may correlate with hepatitis activity in chronic hepatitis C. (+info)
Alanine aminotransferase and glycine aminotransferase from maize (Zea mays L.) leaves.
(58/3443)
Alanine aminotransferase (AlaAT, EC 2.6.1.2) and glycine aminotransferase (GlyAT, EC 2.6.1.4), two different enzymes catalyzing transamination reactions with L-alanine as the amino-acid substrate, were examined in maize in which alanine participates substantially in nitrogen transport. Preparative PAGE of a partially purified preparation of aminotransferases from maize leaves gave 6 fractions differing in electrophoretic mobility. The fastest migrating fraction I represents AlaAT specific for L-alanine as amino donor and 2-oxoglutarate as amino acceptor. The remaining fractions showed three aminotransferase activities: L-alanine-2-oxoglutarate, L-alanine-glyoxylate and L-glutamate-glyoxylate. By means of molecular sieving on Zorbax SE-250 two groups of enzymes were distinguished in the PAGE fractions: of about 100 kDa and 50 kDa. Molecular mass of 104 kDa was ascribed to AlaAT in fraction I, while the molecular mass of the three enzymatic activities in 3 fractions of the low electrophoretic mobility was about 50 kDa. The response of these fractions to: aminooxyacetate, 3-chloro-L-alanine and competing amino acids prompted us to suggest that five out of the six preparative PAGE fractions represented GlyAT isoforms, differing from each other by the L-glutamate-glyoxylate:L-alanine-glyoxylate:L-alanine-2-oxoglutarate activity ratio. (+info)
An outbreak of acute eosinophilic myositis attributed to human Sarcocystis parasitism.
(59/3443)
Seven members of a 15-man U.S. military team that had operated in rural Malaysia developed an acute illness consisting of fever, myalgias, bronchospasm, fleeting pruritic rashes, transient lymphadenopathy, and subcutaneous nodules associated with eosinophilia, elevated erythrocyte sedimentation rate, and elevated levels of muscle creatinine kinase. Sarcocysts of an unidentified Sarcocystis species were found in skeletal muscle biopsies of the index case. Albendazole ameliorated symptoms in the index case; however, his symptoms persisted for more than 5 years. Symptoms in 5 other men were mild to moderate and self-limited, and 1 team member with laboratory abnormalities was asymptomatic. Of 8 team members tested for antibody to Sarcocystis, 6 were positive; of 4 with the eosinophilic myositis syndrome who were tested, all were positive. We attribute this outbreak of eosinophilic myositis to accidental tissue parasitism by Sarcocystis. (+info)
Dirofilaria repens infection in a dog in Israel.
(60/3443)
Only one case of canine infection with Dirofilaria repens has been reported in Israel to date; this occurred in 1934. This publication, 65 years later, represents the second case of D. repens infection in a dog in Israel. This dog was infected locally since it was born in Israel and was never taken abroad, suggesting that the life cycle of the filaria was completed in Israel. Since dogs, cats, and foxes serve as a reservoir for the filaria and these are abundant in Israel, and mosquitoes of the genera Culex and Aedes (both of which occur in Israel and the Middle East) are vectors, the conditions for establishment of the filaria in Israel exist, and warrant regional epidemiologic investigation. (+info)
Activation of caspases in lethal experimental hepatitis and prevention by acute phase proteins.
(61/3443)
Lethal hepatitis can be induced by an agonistic anti-Fas Ab in normal mice or by TNF in mice sensitized to d -(+)-galactosamine or actinomycin D. In all three models, we found that apoptosis of hepatocytes is an early and necessary step to cause lethality. In the three models, we observed activation of the major executioner caspases-3 and -7. Two acute-phase proteins, alpha1-acid glycoprotein and alpha1-antitrypsin, differentially prevent lethality: alpha1-acid glycoprotein protects in both TNF models and not in the anti-Fas model, while alpha1-antitrypsin confers protection in the TNF/d -(+)-galactosamine model only. The protection is inversely correlated with activation of caspase-3 and caspase-7. The data suggest that activation of caspase-3 and -7 is essential in the in vivo induction of apoptosis leading to lethal hepatitis and that acute phase proteins are powerful inhibitors of apoptosis and caspase activation. Furthermore, Bcl-2 transgenic mice, expressing Bcl-2 specifically in hepatocytes, are protected against a lethal challenge with anti-Fas or with TNF/d -(+)-galactosamine, but not against TNF/actinomycin D. The acute-phase proteins might constitute an inducible anti-apoptotic protective system, which in pathology or disturbed homeostasis prevents excessive apoptosis. (+info)
Germ tubes and proteinase activity contribute to virulence of Candida albicans in murine peritonitis.
(62/3443)
Peritonitis with Candida albicans is an important complication of bowel perforation and continuous ambulatory peritoneal dialysis. To define potential virulence factors, we investigated 50 strains of C. albicans in a murine peritonitis model. There was considerable variation in their virulence in this model when virulence was measured as release of organ-specific enzymes into the plasma of infected mice. Alanine aminotransferase (ALT) and alpha-amylase (AM) were used as parameters for damage of the liver and pancreas, respectively. The activities of ALT and AM in the plasma correlated with invasion into the organs measured in histologic sections and the median germ tube length induced with serum in vitro. When the activity of proteinases was inhibited in vivo with pepstatin A, there was a significant reduction of ALT and AM activities. This indicates that proteinases contributed to virulence in this model. Using strains of C. albicans with disruption of secreted aspartyl proteinase gene SAP1, SAP2, SAP3, or SAP4 through SAP6 (collectively referred to as SAP4-6), we showed that only a Deltasap4-6 triple mutant induced a significantly reduced activity of ALT in comparison to the reference strain. In contrast to the Deltasap1, Deltasap2, and Deltasap3 mutants, the ALT induced by the Deltasap4-6 mutant could not be further reduced by pepstatin A treatment, which indicates that Sap4-6 may contribute to virulence in this model. (+info)
Beneficial effects of Mn(III)tetrakis (4-benzoic acid) porphyrin (MnTBAP), a superoxide dismutase mimetic, in zymosan-induced shock.
(63/3443)
1 The therapeutic efficacy of Mn(III)tetrakis (4-benzoic acid) porphyrin (MnTBAP), a novel superoxide dismutase mimetic which scavenges peroxynitrite, was investigated in rats subjected to shock induced by peritoneal injection of zymosan. 2 Our data show that MnTBAP (given at 1, 3 and 10 mg kg-1 intraperitoneally, 1 and 6 h after zymosan injection) significantly reduce in dose dependent manner the development of peritonitis (peritoneal exudation, high nitrate/nitrite and peroxynitrite plasma levels, leukocyte infiltration and histological examination). 3 Furthermore, our data suggest that there is a reduction in the lung, small intestine and liver myeloperoxidase (MPO) activity and lipid peroxidation activity from MnTBAP-treated rats. 4 MnTBAP also reduced the appearance of nitrotyrosine immunoreactivity in the inflamed tissues. 5 Furthermore, a significant reduction of suppression of mitochondrial respiration, DNA strand breakage and reduction of cellular levels of NAD+ was observed in ex vivo macrophages harvested from the peritoneal cavity of zymosan-treated rat. 6 In vivo treatment with MnTBAP significantly reduced in a dose-dependent manner peroxynitrite formation and prevented the appearance of DNA damage, the decrease in mitochondrial respiration and the loss of cellular levels of NAD+. 7 In conclusion our results showed that MnTBAP was effective in preventing the development of zymosan-induced shock. (+info)
Effects of inhibitors of the activity of poly (ADP-ribose) synthetase on the organ injury and dysfunction caused by haemorrhagic shock.
(64/3443)
1 Poly (ADP-ribose) synthetase (PARS) is a nuclear enzyme activated by strand breaks in DNA, which are caused by reactive oxygen species (ROS). Here we investigate the effects of the PARS inhibitors 3-aminobenzamide (3-AB), nicotinamide and 1,5-dihydroxyisoquinoline (ISO) on the circulatory failure and the organ injury/dysfunction caused by haemorrhage and resuscitation in the anaesthetized rat. 2 Haemorrhage (sufficient to lower mean arterial blood pressure to 50 mmHg for 90 min) and subsequent resuscitation with shed blood resulted (within 4 h after resuscitation) in a delayed fall in blood pressure to 66+/-4 mmHg (control, n=13). This circulatory failure was not affected by administration (5 min prior to resuscitation) of 3-AB (10 mg kg-1 i.v., n=7), nicotinamide (10 mg kg-1 i.v., n=6) or ISO (3 mg kg-1 i.v., n=6). 3 Haemorrhage and resuscitation also resulted in rises in the serum levels of urea and creatinine. This renal dysfunction was attenuated by 3-AB and nicotinamide, but not by nicotinic acid (n=7), an inactive analogue of nicotinamide. Although ISO (n=6) also attenuated the renal dysfunction caused by haemorrhage and resuscitation, its vehicle (10% DMSO, n=4) had the same effect. 4 Haemorrhagic shock resulted in enhanced serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lipase, indicating the development of hepatocellular and pancreatic injury, respectively. Similarly, haemorrhagic shock also resulted in an increase in the serum levels of creatine kinase (CK) indicating the development of neuromuscular injury. This was attenuated by 3-AB and nicotinamide, but not by nicotinic acid. Although ISO also attenuated the liver, pancreatic and neuromuscular injury caused by haemorrhagic shock, its vehicle had the same effect. 5 Thus, activation of PARS contributes to the organ injury and dysfunction caused by haemorrhage and resuscitation in the rat. (+info)